Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

<div><p>Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of <i>MMP-2</i> gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the <i>MMP-2</i> gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285–0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365–1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248–1.093). Our study does not exclude the possibility that polymorphisms in <i>MMP-2</i> gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.</p></div

Genotype and Allele Frequencies of <i>Matrix Metalloproteinase-2</i> Gene Polymorphisms in Heart Failure Patients and Healthy Blood Donors.

<p>Genotype and Allele Frequencies of <i>Matrix Metalloproteinase-2</i> Gene Polymorphisms in Heart Failure Patients and Healthy Blood Donors.</p

Baseline Characteristics of Heart Failure Patients According to Self-Reported Ethnicity.

<p>Baseline Characteristics of Heart Failure Patients According to Self-Reported Ethnicity.</p

Kaplan-Meier survival curves in African-Brazilians for all-cause death (A to C) and HF-related death (D to F) according to the -1575G>A, -1059G>A, and -790G>T polymorphisms in <i>MMP-2</i> gene, respectively.

<p>Kaplan-Meier survival curves in African-Brazilians for all-cause death (A to C) and HF-related death (D to F) according to the -1575G>A, -1059G>A, and -790G>T polymorphisms in <i>MMP-2</i> gene, respectively.</p

Kaplan-Meier survival curves in Caucasian- (A and B) and African-Brazilians (C and D) for all-cause death and HF-related death, respectively, according to the <i>MMP-2</i> haplotypes.

<p>Kaplan-Meier survival curves in Caucasian- (A and B) and African-Brazilians (C and D) for all-cause death and HF-related death, respectively, according to the <i>MMP-2</i> haplotypes.</p

Haplotype Frequencies of <i>Matrix Metalloproteinase-2</i> Gene Polymorphisms in Heart Failure Patients and Healthy Blood Donors.

<p>Haplotype Frequencies of <i>Matrix Metalloproteinase-2</i> Gene Polymorphisms in Heart Failure Patients and Healthy Blood Donors.</p